The proposed work seeks firstly to determine the biochemical mechanism for the increased purine and uric acid production in gout, and secondly, to determine if dietary alterations in purine metabolism affect immune function. The approach being taken includes correlating key purine enzyme activities, the net flux of radioactively labelled purines through the purine pathways and total uric acid production under conditions of known and variable uric acid production, as well as impaired immune function. Uric acid production is being altered by dietary manipulation (protein level, absorptive and post-absorptive state). Enzyme, purine flux and total purine production measurements are also being made on cultured skin fibroblasts from humans known to be overproducers of uric acid. Immune function is being assessed by the proliferative response of isolated thymus and spleen lymphocytes to exogenous mitogens.